The main goal of this project is the development and application of an innovative non-invasive in vivo magnetic resonance imaging (MRI) method that represents a new 3D probe of the cytoarchitecture of the developing subcortical white matter (WM) of the unmyelinated preterm human infant brain. The creation of this tool can provide a unique, non-invasive microstructural monitor of both normal WM fiber tract development and the neuronal response to injury. The basic method and its sensitivity to WM injury is clearly demonstrated with preliminary results from preterm infants. The proposed method entails the quantitative determination of the 3D pulsatile extracellular fluid flow field (EFF) within the WM as observed using fast MRI. Its application is, notably, unique to the WM of the early preterm infant group gestational age (GA) approximately <36 weeks, that contains relatively larger extracellular space in unmyelinated WM, and is not now practically observable from the dense myelinated WM of infants GA approximately 40 weeks or adults. Observed pulsatile EFF is forced by the cardiac (arterial pulsation of the brain, an ideal endogenous physiological marker that the investigators exploit. By this method, effects of cardiac pulsation are differentiated by employing a bandpass filter in a Fourier (frequency) analysis of each individual vowel's signal from a fast echo planar dynamic MRI series. By the proposed method, the principal axis and magnitude of the EFF within each vowel will be determined from computations based on MRI time series recorded along each orthogonal direction. It is the hypothesis of this proposed study that the EFF principal flow axis is parallel to the localized intra-voxel WM fiber alignment axis, and the EFF flow magnitude is a function of the WM fiber density and extent of myelination, that is, the EFF directly reveals the subvoxel characteristics of the WM cytoarchitecture. No known non-invasive in vivo technique currently can provide such specific quantitative flow information, noting that Diffusion Tensor MRI contains several different signal contributions combined with that of extracellular water. The new method developed in this study will be applied to acquire and analyze 3D MRI data from 15 preterm infants and two term infants in each of two years, and produce a 3D visualization of the 3D EFF in each case. Results will be analyzed in conjunction with 3D DT-MRI results and segmentation results also obtained in each case to prove the hypothesis that EFF reveals quantitative details of WM cytoarchitecture. Further method refinements are planned.